Pesticides based on vicinal diols

ABSTRACT

Pesticides based on vicinal diols, are available to control arthropod ectoparasites such as  Pediculus Humanus, Dermatophagoides pteronyssinus, Musca domestica , the Blattidae,  Blatella Germanica , and  Periplaneta Americana , by introducing to the locus of an infestation of the pest, a composition containing as active ingredient a vicinal diol.

This is a nationalization of PCT/GB02/00825 filed Feb. 28, 2002 andpublished in English.

This invention relates to the use of hydroxy-substituted hydrocarbylcompounds, particularly vicinal diols such as 1,2-alkyldiols to controlarthropod pests.

BACKGROUND TO THE INVENTION

There is a need for a class of pesticidal agents that is able to kill awide range of common arthropod pests of humans, their companion animalsand livestock, notably those belonging to the phyletic classes Arachnida(ticks and mites) and Insecta (cockroaches, fleas, flies, silverfish,lice). Given the intimate nature of the association of these parasiteswith their human or animal hosts, such agents must, for any practicalpurpose, be relatively non-toxic to the host. There is a further needfor a class of pesticidal agents that is able to kill a wide range ofarthropod pests on foliage, in the agriculture and garden sectors.

It is also advantageous that the pesticide in either case isecologically-friendly (i.e. biodegradable).

A large number of chemical compounds have been developed and marketed aspesticidal agents. However, few satisfy the triple criteria (1)generalised toxicity to arthropod pests; (2) comparatively low toxicityto human and animal hosts and (3) good biodegradability.

OBJECTS OF THE INVENTION

An object of the present invention is to provide alternative pesticidalagents that will obviate or mitigate at least some of the drawbacks ofcurrently commercially available products. In particular it is an objectto provide a method of control of arthropod.

SUMMARY OF THE INVENTION

Now it is discovered that vicinal diols satisfy the desired criteriavery well. In particular, the current research has revealed that certaincompounds of the class of vicinal diols which have the chemical formula,R(OH)₂, wherein the hydroxyl groups occupy vicinal positions and R is ahydrocarbyl chain that is optionally derivatised or substituted, offerremarkably good efficacy as pesticides of the desired qualities. Thelimiting number of carbons in the R group is a matter of ongoingresearch. However, good results are observed where the compound has atleast one hydrocarbyl chain of length n+2 atoms, wherein the value of nis preferably at least 2 carbons, and the vicinal hydroxyls occupy aterminal position, preferably having hydroxyls at 1,2-positions suchthat the diol forms a head group with a lipophilic tail. Differingactivities are observed with changes in n value. This leads topreferences amongst them and differences in activity for lower alkylgroups in comparison with higher alkyl groups (C₆ and above). Thus n mayhave a value of up to 20, but compounds wherein n has a value of from 2to 12 inclusive are of particular interest currently. Such diols arechiral in nature with, for example, the second carbon being a chiralcentre in the case of 1,2 diols. A racemic mixture is usefully employedin the present invention but single optical isomers (enantiomers), ormixtures containing a preponderance of one or more particular opticalisomer(s) can also serve the purposes of the invention. For example bothenantiomers of 1,2-decanediol have been shown to be effective againstlice in comparable fashion to the racemic mixture whose results aretabulated hereinafter.

The use of 1,2-alkyldiols for the control of bacterial infection hasalready been shown. Kazunori (Japanese patent application No. JP 50-15925/Publication No. 51-91 327) teaches that 1,2-alkyl diols, especiallymedium-chain homologues (n=5−9), are efficient bacteria- andfungi-static agents with general application. Similarly Pugliese (U.S.Pat. No. 4,049,830) teaches the application of 1,2-alkyl diols for thesterilisation of bovine teats as a prophylactic treatment for bacterialbovine mastitis. Similarly Greff (U.S. Pat. No. 6,123,953) teaches theuse of 1,2-diols for generalised topical application in the control ofbacteria that cause skin ailments including mastitis, acne and dandruff.Similarly Agostini and Cupferman (European patent application EP 0 935960 A1) teach cosmetic formulations containing an 1,2-alkyl diol as anantibacterial agent.

Airs in GB 687 850 has taught the use of certain vicinal diols as insectrepellents together with known non-solvent insecticides. The potentialfor the application of vicinal diols as the active ingredient in thecontrol of pests by killing them or their ova has not heretofore beenconsidered. Lover and Singer et al (U.S. Pat. No. 4,368,207) teach theuse of a range of monohydric alcohols against lice, their ova, andmites. Similarly Lover and Singer et al teach the use of non-vicinal,particularly 1,3 diols, in United Kingdom patent UK 1 604 856. Thatpatent suggests such compounds for the control of ectoparasites andtheir ova.

It has now been discovered that vicinal diols, in a preferred embodimentthe readily available 1,2 diols, have surprisingly enhanced pesticidalproperties in comparison with mono-ols or non-vicinal diols.1,2-Alkyldiols may be used to kill a wide range of common arthropodpests, notably arachnids, such as ticks and mites, and insects, such asflies, cockroaches, silverfish and lice, and ovicidal effects can bedemonstrated. Moreover these are found to be biodegradable, andeminently suitable as valuable pesticides for a wide variety of uses andapplications.

Whilst the potency and efficacy of the vicinal diols per se is proven,so that the selected diols themselves are directly useful, in most casesthe target pests can be effectively combated with diluted amountsthereof, and for some purposes preferred delivery forms will offeradditional technical advantages.

Accordingly, further according to the invention there are providedformulations that are suitable for contact application of such vicinaldiols or their derivatives, comprising at least one such vicinal diol ina physiologically tolerable carrier, for the control of specificpest-induced ailments of humans and animals, including head- orbody-louse infection, carpet mite infestation, sheep-scab mite infectionand blow-fly strike.

Typically the formulations will comprise compositions of the preferredvicinal diols alone or in combination, together with suitableauxiliaries as required, with a carrier adapted to deliver an effectiveamount of the vicinal diol(s) to the locus of a pest infestation. Thecarrier will usually be selected with a view to prolonging contact withthe target pest. Depending upon the infestation targeted, the carriermay be a finely divided solid or a liquid, and may be selected frompowder, resins, and aqueous or organic fluids. Therefore, a suitableformulating aid may be selected from liquid vehicles, solid carriers,auxiliaries, emulsifiers, dispersants, resins, gums, adherents, diluentsand extenders.

The pesticidal composition may be suitably prepared for delivery in aformulation selected from a solution, a dispersion, an emulsion, adusting powder, a paste, an aerosol, a cream, a foam, a coated substratee.g. tacky paper, a pellet or block e.g. as in a bait for a trap. Theskilled worker will observe the need to select a physiologically benignor tolerable carrier when the pest is to be combated directly upon alive host, and may select such carriers from pharmaceutically acceptablecarriers, especially those intended for topical application, to formcreams, gels, pastes and ointments, aerated (foam/mousse) compositionsor dusting powders e.g. talc.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will now be described in more detail by way of examplewith reference where appropriate to the accompanying drawings in which:

FIG. 1 is a graph of LC₅₀ values found for a range of 1,2 diols againstthe human body louse (Pediculus humanus); and

FIG. 2 is a further graph illustrating a relationship between diol chainlength and egg-laying activity of treated lice.

The following results will serve to illustrate the utility of selectedvicinal diols against a range of pests but should not be considered toprescribe limits to their effectiveness against these or otherorganisms. Demonstration of efficacy of the selected vicinal diolsherein is not intended to exclude analogues thereof except as may bespecifically stated herein and attention is directed to the claimshereinafter which define the scope of the invention.

EXAMPLE 1

Efficacy Contra Pediculus humanus

The pesticidal efficacy of compositions provided by this invention isdemonstrated firstly with regard to the human body louse (Pediculushumanus), using vicinal diols in tests according to accepted industryprotocols.

The special value and unique nature of vicinal diols is illustrated inTables 1 and 2 wherein the LC₅₀ values, measured in tests against lice,for a range of diols and mono-ols are tabulated. Table 1 shows thesurprising potency of the vicinal diols in comparison to 1,3 and othernon-vicinal diols. For example 1,2-decanediol is significantly superiorto 1,3-decanediol and the benefit of the vicinal compounds is apparentin the Table for all the examples of chain length shown.

Table 2 shows similar superiority of the vicinal diols over mono-ols andsome triols. The best mono-ol tested has only 36% of the potency foundfor 1,2-decanediol. The superior potency of the vicinal diols providesthe benefit that they can provide effective control of a pest even whenapplied in a less than ideal manner to the target organisms. A yetfurther benefit of these compounds is that they have been shown to bereadily metabolised by common soil bacteria, derived from severaldifferent locations, and so will biodegrade readily when dispersed inthe environment.

TABLE 1 LC₅₀ value Potency index* Compound Diol Type (mMol) (%)1,2-Butanediol Vicinal >700 Not effective 1,3-ButanediolNon-vicinal >2000 Not effective 1,2-Hexanediol Vicinal >200  61,5-Hexanediol Non-vicinal Not calculable Not effective 1,6-HexanediolNon-vicinal Not calculable Not effective 2,5-Hexanediol Non-vicinal Notcalculable Not effective 1,2-Octanediol Vicinal 40  30 1,3-OctanediolNon-vicinal >400 Not effective 1,2-Decanediol Vicinal 12 1001,3-Decanediol Non-vicinal 40  30 *The potency index compares the LC₅₀value found with that of 1,2-decanediol (=100%)

TABLE 2 LC₅₀ value *Potency Index Compound (mMol) (%) 1,2,3-HexanetriolNot calculable Not effective 1,2,6-Hexanetriol Not calculable Noteffective 2-Ethyl-1-hexanol 300  4 2-Ethyl-1,3-hexanediol  60  201-Decanol  35  32 2-Decanol  37  34 4-Decanol 183  6 9-Decene-1-ol  33 36 1,2-Decanediol  12 100 3-Ethyl-1-decanol  62  203-Octyl-1,2-decanediol  97  12 3-Ethyl-1,2-decanediol Not calculable Noteffective *The potency index compares the LC₅₀ value found with that of1,2-decanediol (=100%).

The effect of diol chain length on activity is illustrated in FIG. 1, byway of a graph of the LC₅₀ values found for a range of 1,2 diols againstthe human body louse.

These results show that 1,2 diols have pediculicidal activity, to theextent that C₄ to C₁₆ diols are active, and those from C₈ to C₁₄ arepreferred, with the most preferred being 1,2-octanediol, 1,2-decanedioland 1,2-dodecanediol.

FIG. 2 demonstrates a further a beneficial property of the subjectmatter of the invention, namely the inhibition of egg laying, animportant feature in that the life cycle of the target organism isinterrupted when egg laying is inhibited or stopped. This is observed byconsidering the graphic illustration of efficacy of a range of diolswhich shows that as diol chain length increases egg laying activity oftreated lice declines substantially. 1,2-Octanediol is especiallyefficacious in the prevention of egg laying.

Ovicidal activity has been observed but research on this aspect ofactivity is continuing and the data is not included in this submission.

EXAMPLE 2

Efficacy Contra Dermatophagoides pteronyssinus

The utility of the vicinal diols is further illustrated by the resultsof experiments against the house dust mite Dermatophagoidespteronyssinus according to accepted industry protocols. Mites weresealed in a cotton envelope and briefly immersed (5 seconds) in dilutesolutions (2.5%) of selected diols. The mites were examined one hourafter immersion and mortality calculated. The results are shown in Table3 below with comparative results for a proprietary carpet shampoo,permethrin insecticide and water (as controls).

TABLE 3 Mortality Treatment (%) 1,2-Octanediol 65 1,2-Decanediol 95Water 3 3% carpet shampoo 3 0.25% Permethrin 100

EXAMPLE 3

Efficacy Contra Musca domestica

A further example of the use of the compounds of the present inventionis shown by testing decane-1,2-diol against house flies in a standardindustry protocol for insecticides. More than 80% mortality was observedafter 24 hours contrasting with decane-1,10-diol which did not exhibitinsecticidal activity.

EXAMPLE 4

Formulation and Application

Vicinal diols are readily formulated in aqueous systems using non-toxicco-solvents such as isopropyl alcohol or by use of surfactants such asTween®. This makes them eminently suitable for inclusion into manyhousehold or industrial, pesticidal or cleansing products. In particularthey can be incorporated into pharmaceutical preparations for use onhumans or animals. The treatment of lice and cockroaches withformulations containing 1,2-octanediol or 1,2-decanediol is tabulated inTable 4 along with control results for the solvent systems employed. Ina procedure following standard industry protocols the subject animalswere immersed for a few seconds in the test formulations and blotteddry. Mortality after 24 hrs was measured for the lice, after 1 hr forthe cockroaches.

TABLE 4 Lice mortality Cockroach mortality Treatment after 24 hr (%)after 1 hr (%) 1,2-Octanediol in 100 100 1.5% Tween20 ® 1,2-Octanediolin 50% 100 100 isopropyl alcohol 1,2-Decanediol in 7% 100 100 Tween20 ®1,2-Decanediol in 50% 100 100 isopropyl alcohol 0.25% Permethrin in 100100 Water Water 4 0 50% isopropyl alcohol 4 0 1.5% Tween20 ® 0 0 7%Tween20 ® 13 0

INDUSTRIAL APPLICABILITY

In view of the aforesaid advantages and pesticidal properties of thecompounds used in the compositions described herein, the invention willbe usefully applied in dealing with pests encountered in agriculture,horticulture, human health, hygiene and veterinary medicine.

1. A method of treating an infestation of lice by killing the lice orrendering the lice moribund, comprising (1) locating a lice infestationor their ova, and (2) applying to the lice infestation or their ova aneffective amount of at least one vicinal diol R(OH)₂, wherein thevicinal diol is selected from the group consisting of unbranched,unsubstituted aliphatic 1,2-vicinol diols having an aliphatic chaincomprising 8-14 carbon atoms.
 2. The method of claim 1, wherein the liceinfestation comprises a head louse infestation.
 3. The method of claim1, wherein the lice infestation comprises a body louse infestation. 4.The method of claim 1, wherein the arthropod infestation comprises aninfestation of Pediculus humanus.
 5. The method of claim 1, wherein thevicinal diol is selected from the group consisting of unsubstitutedaliphatic 1,2-vicinol diols having an aliphatic chain comprising 8-12carbon atoms.
 6. The method of claim 5, wherein the vicinal diolcomprises 1,2-octanediol.
 7. The method of claim 5, wherein the vicinaldiol comprises 1,2-decanediol.
 8. The method of claim 5, wherein thevicinal diol comprises 1,2-dodecanediol.
 9. The method of claim 1,wherein the vicinal diol is applied as a composition consistingessentially of the vicinal diol and at least one physiologicallytolerable carrier.
 10. The method of claim 6, wherein the vicinal diolis applied as a composition consisting essentially of the vicinal dioland at least one physiologically tolerable carrier.
 11. The method ofclaim 5, wherein the arthropod infestation comprises an infestation ofPediculus humanus.